patients with malignant ascites due to advanced-stage gastro-intestinal cancers MedDRA version: 14.1 Level: PT Classification code 10017758 Term: Gastric cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: LLT Classification code 10015362 Term: Esophageal cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 14.1 Level: LLT Classification code 1
Conditions
Interventions
Trade Name: Avastin
Product Name: Bevacizumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Bevacizumab
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
AIO Studien gGmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years 2. Written informed consent has been obtained prior to inclu¬sion into the study 3. Patient is capable and willing to comply with the study 4. Histologically confirmed esophageal, gastric, pancreatic, cholangiocellular, hepatocellular, or colorectal carcinoma 5. Cytologically confirmed ascites OR diagnosis of an exsudate (total protein in ascites > 30 g/l) clinically suggestive for malignant ascites OR morphological diagnosis of peritoneal carcinosis by CT , MRT or ultrasound 6. Ascites clinically judged as not responsive to conventional systemic therapies for primary malignancy 7. Ascites clinically judged as not responsive to diuretics 8. At the time of inclusion paracentesis required at least once within past 4 weeks. The first application of study medication must not take place later than 4 weeks after the preceding paracentesis in screening phase. 9. Before inclusion of the patient into the study, a 4-week screening period will allow for a stringent evaluation of the patient regarding fulfillment of inclusion and exclusion criteria. Importantly, no treatments for malignant ascites other than paracentesis and diuretics are allowed during the 4-week screening period. 10. ECOG performance score 0-3 11. Life expectancy > 12 weeks 12. Laboratory parameters: Hematology • Neutrophils > 1,500/µl • Platelets > 100,000/µl • Hemoglobin >= 9 g/dl or 5.59 mmol/l Hemastasiology • INR 30 ml/min, serum creatinine = 2+ proteinuria on dipstick urinalysis, who demonstrate =65 years) yes F.1.3.1 Number of subjects for this age range 72
Exclusion criteria
Exclusion criteria: 1. Concomitant malignancies other than gastrointestinal cancers (Patients with curatively treated basal and squamous cell carcino¬ma of the skin and / or in-situ carci¬noma of the cervix are eligible). 2. Bacterial peritonitis as indicated by laboratory results (neutrophil count > 250 / µl ascites) or clinical suspicion 3. Hemorrhagic ascites (ascites hematocrit > 2%) 5. Parallel treatment with anti-tumor agents other than the study medication from inclusion into the study until safety follow-up. Chemotherapy may be continued if started before screening phase (– 4 weeks before inclusion). Parallel Treatment with Bevacizumab i.v. is not allowed. 6. Therapy naïve patients 7. Parallel treatment of ascites with measures other than paracentesis, diuretics, and the study drugs from 4 weeks before inclusion into the study until safety follow-up. 8. Patients with extensive metastases of the liver making up > 70% of the total liver mass 9. Child C cirrhosis of the liver 10. Occlusion or thrombosis of the portal vein. 11. Evidence of current and symptomatic central nervous system (CNS) metastases or spinal cord compression. 12. 12. Clinically significant cardiovascular diseases, e.g., un¬con¬trolled hypertension, uncontrolled arrhythmia, hemoptoe, cardiovascular accident within the last 6 months before treatment start, unstable angina, congestive heart failure (CHF) NYHA grade III/IV, symptomatic coronary heart disease, peripheral arterial disease stage >= II. 13. History of fistula formation involving an internal organ (e.g. tracheo-oesophagal, bronchopleural, biliary, vagina and bladder) 14. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study. 15. Concomitant treatment with intravenous Bevacizumab for primary malignancy from inclusion into study until safety follow-up, Prior treatment with Bevacizumab for primary malignancy is not exclusionary. 16. Serious non-healing wound, ulcer or bone fracture. 17. Radiotherapy for purposes other than local control of symptoms. 18. Evidence of bleeding diathesis or coagulopathy. 19. Hematopoietic diseases. 20. Known intra-abdominal inflammatory process or serious gastrointestinal ulceration. 21. History of chronic intestinal diseases associated with severe diarrhea. 22. Thrombo-embolic events or severe hemorrhage ( 1.5) oral coumarin-derived anticoagulants, the use of full dose anticoagulants is allowed as long as the INR or a PTT is within therapeutic limits (according to the medical standard in the institution) and the patient has been on a stable dose for at least two weeks at the time of randomisation. 26. Patients who participated within the last 30 days prior to enrolment in a clinical trial and received a non approved investigational drug (e.g. follow up within the trial is not exclusionary). 27. Patients who have participated in this study before. 28. Women, lactating, pregnant or of childbearing potential and fertil
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the paracentesis-free survival (ParFS) following intraperitoneal application of Bevacizumab/Placebo ;Secondary Objective: • To measure the frequency of paracenteses required for symptom control following intraperitoneal application of Bevacizumab/Placebo, by assessing the longest paracen¬tesis-free period within the 12-week main observation period (“best response”) • To measure the volume of ascites following intraperitoneal application of Bevacizumab/Placebo • To measure the effect of study treatment on the quality of life • To assess feasibility and safety of intraperitoneal application of Bevacizumab including pharmakocinetic of Bevacizumab • To evaluate the effect of an intraperitoneal application of Bevacizumab/Placebo on serum and ascites VEGF concen¬trations ;Primary end point(s): Efficacy: • Paracentesis-free survival (ParFS), i.e. the time period between the initial puncture after randomization to the first subsequent paracentesis or other symptomatic treatments for ascites with the exception of diuretics or until death (whichever occurs first) ;Timepoint(s) of evaluation of this end point: at the first subsequent paracentesis after the initial puncture | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): best response representing the longest period of time (in days) from one paracentesis until next paracentesis within the treatment period or, if longer, from the last paracentesis performed within the treatment period until first subsequent symptomatic treatment for ascites or, if longer, from the last paracentesis performed within the treatment period until death or, if longer, from the last paracentesis performed within the treatment period until 4 week follow-up. Volume of ascites drained by routine paracentesis Total volume of ascites as indicated by body weight Quality of life as assessed by standardized questionnaires Number of patients with CR/PR;Timepoint(s) of evaluation of this end point: at each paracentesis | — |
Countries
Germany
Contacts
Public ContactPD Dr. Ullrich Graeven
AIO Studien gGmbH
Outcome results
None listed